Naloxone prevention of morphine LDR curve flattening associated with high-dose tolerance.
Male wistar rats, previously made tolerant to morphine by at least 3 weeks of daily intraperitoneal (IP) injections of 20 mg/kg morphine-SO4 (MS), were then given 200 mg/kg MS daily for 4 or 5 days. Tail immersion tests of antinociception, carried out before and after the 200 mg/kg MS treatment, indicated that the additional morphine treatment, was followed by a large further decrease in opiate sensitivity, characterized by decreased slope of the log-dose/response curve (LDR curve flattening). The further decrease in opiate sensitivity was substantially reduced by naloxone-HCl (IP) in a dose of 10 mg/kg given 30 min before and 8 h after the 200 mg/kg MS injections, or a dose of 4 mg/kg given 45 min after the MS. It was concluded that LDR curve flattening produced by high doses of MS is mediated by specific opiate receptors, and is a true expression of a high degree of opiate tolerance in the intact rat.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009270:Naloxone / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D009270:Naloxone; D009020:Morphine